Tiny worms employed to unlock keys to herbal medicines

"This provides the first step to find, from all of the hundreds of compounds in herbs, which ones have potential for medicinal purposes. And you can do this very quickly and efficiently," said co-author Laura Dosanjh, graduate student with the School of Pharmacy at UMB.

Science has not been very helpful in determining the efficacy of herbal medicines in the United States. The U.S. Food and Drug Administration, for example, has so far sided with science only once to approve an herb-based treatment with multiple active ingredients -- an ointment for genital warts made from green tea leaves.

Now, using tiny worms that live only 20 days, the team sorted out which compounds found in two common Chinese herbal formulations showed most potential for their stated purpose: extending life expectancy.

Cinnamon and ginseng won, showing the most promise.

A team led by Yuan Luo PhD, MS, associate professor at the School, conducted a first-of-its- kind, "systematic evaluation" of a mixture of 10 herbs called Shi-Quan-Da-Bu-Tang (SQDB), reportedly effective for fatigue and energy; and an 11-herb formula called Huo Luo Xiao Ling Dan (HLXL) used as a the treatment of arthritic joint pain. Both mixtures are reputed to have benefits for healthy living and longevity in humans.

The researchers tested the mixtures, as well as each separate herb in them, on the laboratory worm model C. elegans. This particular worm─which biochemists often use as their 'lab rat'─ shares genes for aging and other traits with humans and other organisms.

Cinnamon bark (Cinnamomum cassia) from HLXL extended life span of the worms by 14.5 percent and cinnamon bark from SQDB extended the life 10.8 percent.

Ginseng root (Panax ginseng) from SQDB extended life span by 7.7 percent. Ginseng is not an ingredient in HLXL.

Significantly, cinnamon, ginseng, and SQDB also thinned out levels of hydrogen peroxide, which can destroy cells. They each also enhanced expression of small heat shock proteins, an indicator for cellular response to stress that plays an important role in maintenance of cell functions.

Furthermore, the life span-extending herbs appreciatively reduced in the expression in C. elegans of a toxicity factor, amyloid, which is a hallmark in the human brain of pathological development of Alzheimer's disease.

In a 1998 national survey published in the Journal of American Medical Association, 49 percent of American adults said they had used herbal medicines within the previous year. However, proof of efficacy of herbal medicines, even their modes of action in the body, are extremely difficult challenges, said, Luo.

Herbal medicines are usually mixtures of herbs. That presents a severe challenge for the Food and Drug Administration to understand which compounds or combinations of compounds in the herbs are effective or not effective.

Said Dosanjh, "Because it's very difficult to sort out so many herbs with so many constituents together, we needed to find a model. And there is a high level of [common genetic origins] with the nematode and humans."

Luo added, "To isolate a single compound from an herb and test it for a medical condition, it often doesn't work; not like the whole herb works."

In recent years, scientists have learned to use C. elegans worm as a model system in for studying gene-environment interactions. In their experiments, the School of Pharmacy researchers first used "wild" C. elegans to screen the herbal mixtures and single herbs. They determined which herbs aided lifespan of the worms, then tested those herbs on well-characterized mutant worms. Each mutant was missing a single gene known for lifespan and/or stress resistance. C. elegans is valuable to science because its very short life cycle is suitable for conducting rapid experiments and between 60 to 80 percent of the 20,000 genes in C. elegans genome have similar origins to human genes. The genes are found consistently along the evolutionary paths including the worms and humans.

"The good news is that this is a way of testing to show the medicinal effect. It is now testable. We have statistical evidence for the first time in C. elegans for a multi-compound drug," said Luo. "Most [scientists] are not using whole organisms for screening herbs. This is simple and clean, it is a system to look at specific genes. Now we have to further validate the human relevancy.

The School of Pharmacy study was published in the Feb. 2010 issue of PLoS ONE, Vo. 5.